Products
Diroximelfumarate was approved in the United States in 2019 in the form of sustained-release capsules (Vumerity). It should not be confused with dimethyl fumarate (Tecfidera).
Structure and properties
Diroximelfumarate (C11H13NO6, Mr = of 255.2 g/mol) exists as a white powder that is sparingly soluble in water. The active metabolite monomethyl fumarate (MMF, see below) is esterified with 2-hydroxyethyl succinimide (HES).
Effects
Diroximelfumarate is an ester prodrug that is hydrolyzed by esterases to its active metabolite monomethyl fumarate (MMF). This is the same metabolite formed from dimethyl fumarate (Tecfidera). However, diroximelfumarate releases less methanol. The half-life of the active metabolite is about one hour. Diroximelfumarate has immunomodulatory, anti-inflammatory, and neuroprotective properties. The effects are thought to be due to activation of the Nrf2 (nuclear 1 factor (erythroid-derived 2)-like 2 antioxidant response pathway). This is an important cellular mechanism against the cell-damaging effects of oxidative stress and the inflammatory response.
Indications
For the treatment of multiple sclerosis.
Dosage
According to the SmPC. The capsules are taken twice daily (morning and evening). They should not be administered with a meal containing a high percentage of fat or with high-calorie food.
Contraindications
- Hypersensitivity
- Concurrent treatment with dimethyl fumarate
For complete precautions, see the drug label.
Interactions
Diroximelfumarate should not be taken with dimethyl fumarate or with alcohol. Diroximelfumarate does not interact with CYP450 isoenzymes.
Adverse effects
The most common potential adverse effects include flushing, abdominal pain, diarrhea, and nausea. Compared with dimethyl fumarate, diroximel fumarate is characterized by better gastrointestinal tolerability.
